Worman Howard J, Courvalin Jean-Claude
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Clin Invest. 2004 Feb;113(3):349-51. doi: 10.1172/JCI20832.
Mutations in lamins A and C, nuclear intermediate-filament proteins in nearly all somatic cells, cause a variety of diseases that primarily affect striated muscle, adipocytes, or peripheral nerves or cause features of premature aging. Two new studies (see the related articles beginning on pages 357 and 370) use lamin A/C-deficient mice, which develop striated muscle disease, as a model to investigate pathogenic mechanisms. These reports provide evidence for a stepwise process in which mechanically stressed cells first develop chromatin and nuclear envelope damage and then develop secondary alterations in the transcriptional activation of genes in adaptive and protective pathways.
核纤层蛋白A和C是几乎所有体细胞中的核中间丝蛋白，其突变会引发多种主要影响横纹肌、脂肪细胞或周围神经的疾病，或导致早衰特征。两项新研究（见第357页和第370页开始的相关文章）使用患有横纹肌疾病的核纤层蛋白A/C缺陷小鼠作为模型来研究致病机制。这些报告为一个逐步过程提供了证据，在这个过程中，受到机械应力的细胞首先出现染色质和核膜损伤，然后在适应性和保护途径中的基因转录激活方面出现继发性改变。
